OPTIMALVAC (project completed)

Initiative on Optimising Malaria Vaccine Lab Assays Evaluation

Background 
OPTIMALVAC_presentation_101126

A broad range of malaria vaccine candidates, derived from a diverse set of technologies, has been created from the multiple approaches being taken by different groups in developing malaria vaccines. The majority of vaccine candidates are recombinant proteins based on complex native antigens found on the surface of the parasite. The vaccine potential of these parasite surface antigens is often supported by epidemiological data, and by the ability to induce measurable antigen-specific antibodies or potential protective responses in animals, and later in humans. In vivoassays such as protection models in mice or non-human primates, as well as human sporozoite challenge, provide additional data for some relevant antigens (e.g. pre-erythrocytic antigens).

Individual groups have developed assays within the context of their vaccine discovery efforts, with identification of measurable processes for parasite growth and virulence to test specific antigens. In-house assays are strain-, stage- and even process-specific, and the ability to compare results between different candidates is further limited by diverse methodologies and assay components such as parasites, cells and reagents. The lack of harmonisation of malaria vaccine assays leads to scepticism about the comparability of assay results that in turn generate controversy and uncertainty about the efficacy of the vaccines. Thus, efforts must be made to develop a baseline level of standardisation around key assays that can be utilised, firstly in the evaluation of malaria vaccines, and secondly throughout the development process.

Objectives

The overall goal of this three year project is to develop harmonised assays for parasite antigen recognition, cell-dependent parasite inhibition and cell-mediated immune responses through application of a framework approach to a harmonised assay:

  1. To develop, disseminate and implement Standard Operating Procedures (SOP) for the conduct of key assays up to Good Laboratory Practice (GLP) level;
  2. To develop and share reference preparations and common reagents;
  3. To develop, establish and make available a core set of resources and skills essential for achieving the goal of collaborative action;
  4. To develop and establish a web-based tool for communication and tracking of activities.

Consistent, reproducible and comparable intra- and inter-lab performance and increased accuracy and precision of assay data will strengthen the quality of the data on vaccine performance and generate greater confidence in the vaccine potential of the vaccine candidate.

This is achieved through eight work packages (WP):

WP1 Recognition of parasite proteins by antibodies
WP2 Cell-Dependent Parasite Inhibition (CDPI) assays
WP3 Assays assessing Cell-Mediated Immune (CMI) responses
WP4 Repository of resources
WP5 Data management, statistical analysis and dissemination
WP6 Regulatory and ethical considerations
WP7 Project coordination and management
WP8 Global project coordination and management

Major Milestones

Month 9: Key parameters, acceptance criteria reference cell preparations and reagents for CMI response assays identified.
Month 15: Harmonised SOP for CMI response assays available to all participants.
Month 24: Control reagents and harmonised protocols for parasite antigen recognition available.
Month 24: Consensus SOP for CDPI assays available.
Month 26: Standard reagents, sera and IgG fractions for CDPI assays available for distribution and testing.
Month 28: Database and repository(ies) of facilities and material resources available.

Research Reagent Repository

The OPTIMALVAC Research Reagent Repository may be accessed by following the link www.malariaresearch.eu.

Tools for Data Management and Analysis

Protocols/SOPs:
Routine Culturing of Plasmodium falciparum - UEDIN
Growth Inhibition Assay (GIA) - UEDIN
Growth Inhibition Assay (GIA) - BPRC 
Antigen Reversal GIA - BPRC 
ELISA - UEDIN
ELISA - BPRC 
Immuno-Fluorecence Assay (IFA) - UEDIN 
Avidity ELISA
Competition ELISA 
Measles ELISA
2 cycle GIA with pLDH assay 
OPTIMALVAC IFA protocol

GIA Data Analysis and Management Application:
GIADAMA is a data analysis package for the parasite growth inhibition assays (GIA)

GIADAMA Software Tool

Auditable Data Management System for Elisa:
ADAMSEL FPL is an application that converts OD readings obtained from ELISA plate readers into concentrations by four-parameter fitting and ADAMSEL Merge is an application to merge results generated by ADAMSEL FPL. They are designed to provide an auditable system that minimises data handling, thereby reducing the chances for error.

ADAMSEL Manual
Software Tool 1 (ADAMSEL FPL v1.1)
Software Tool 2 (ADAMSEL MERGE v1.1)

References:                                           

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  1. OPTIMALVAC Consortium: Towards validated assays for key immunological outcomes, Vaccine (Epub 4 Feb 2011), DOI: doi:10.1016/j.vaccine.2011.01.070
  2. Vasee S Moorthy and Marie Paule Kieny: Reducing Empiricism in Malaria Vaccine Design, Lancet Infect Dis. 2010 Mar;10(3):204-11.

Publications

Vaccine (Epub 4 Feb 2011), DOI: doi:10.1016/j.vaccine.2011.01.070